Endomentrial cancer includes all forms and subtypes of the disease, including for example, serous, mucinous, and endometrioid histological subtypes or any other cancer that starts in the endometrium, which includes the lining of the uterus. Particularly, cancer of the endometrium is the most common gynecologic malignancy and accounts for 6% of all cancers in women.
Members of the fibroblast growth factor receptor (FGFR) tyrosine kinase family have been shown to be amplified or mutationally activated in endometrial cancer and a variety of other cancer types, including breast cancer, ovarian cancer, lung cancer, gastric cancer, bladder cancer, glioblastoma and rhabdomyosarcoma, making FGFRs an attractive potential therapeutic target. Targeted tyrosine kinase inhibitors (TKIs) have shown success in cancer treatment. However, the long-term efficacy of these TKIs is frequently limited by development of resistance to the TKIs. The resistance developed to TKIs can be due to mutation of the target kinase. Therefore, there is a need to determine specific resistance profiles for each particular compound by discovering relevant mutation(s) in FGFR. Such FGFR mutation(s) can be used to develop a companion test of a drug, i.e., screening for susceptibility to a FGFR inhibitor. The identification of specific TKI-resistant FGFR mutations is also required to develop second generation inhibitors, whether it is an FGFR-specific inhibitor, or a multi-targeted protein kinase inhibitor, or a combination of selective antagonists, as in an anti-tumor or anti-cancer drug.